A study of the conformational flexibility of the myelin basic protein has shown that the molecule is not stabilized to any significant extent by intramolecular interactions. As the net charge on the molecule increases from nearly zero at pH 11 to +41 at pH 2-3, the molecule gradually expands with no evidence of a cooperative transition. At pH 2 or pH 7 the molecule continually contracts as the ionic strength increases. Relatively low concentrations of guanidine hydrochloride are sufficient to cause an expansion of the protein with no evidence of a cooperative transition. There appears to be very little structure in the molecule which is stable to changes in the external milieu. This conformational flexibility of the protein may be necessary for maximal interaction of the protein with lipids in the myelin sheath.